Deaths and cardiopulmonary events following colorectal cancer screening—A systematic review with meta-analyses

Background Colorectal cancer screening programmes (CRCSPs) are implemented worldwide despite recent evidence indicating more physical harm occurring during CRCSPs than previously thought. Therefore, we aimed to review the evidence on physical harms associated with endoscopic diagnostic procedures during CRCSPs and, when possible, to quantify the risk of the most serious types of physical harm during CRCSPs, i.e. deaths and cardiopulmonary events (CPEs). Methods Systematic review with descriptive statistics and random-effects meta-analyses of studies investigating physical harms following CRCSPs. We conducted a systematic search in the literature and assessed the risk of bias and the certainty of the evidence. Results We included 134 studies for review, reporting findings from 151 unique populations when accounting for multiple screening interventions per study. Physical harm can be categorized into 17 types of harm. The evidence was very heterogeneous with inadequate measurement and reporting of harms. The risk of bias was serious or critical in 95% of assessments of deaths and CPEs, and the certainty of the evidence was very low in all analyses. The risk of death was assessed for 57 populations with large variation across studies. Meta-analyses indicated that 3 to 23 deaths occur during CRCSPs per 100,000 people screened. Cardiopulmonary events were assessed for 55 populations. Despite our efforts to subcategorize CPEs into 17 distinct subtypes, 41% of CPE assessments were too poorly measured or reported to allow quantification. We found a tendency towards lower estimates of deaths and CPEs in studies with a critical risk of bias. Discussion Deaths and CPEs during CRCSPs are rare, yet they do occur during CRCSPs. We believe that our findings are conservative due to the heterogeneity and low quality of the evidence. A standardized system for the measurement and reporting of the harms of screening is warranted. Trial registration PROSPERO Registration number CRD42017058844.


Figure 4 .
Figure 4. Green colour represents subpopulations with low risk of bias for the type of bias, yellow; moderate risk of bias, red; serious risk of bias and black; critical risk of bias.The distribution is weighted according to the size of each of the subpopulations.

Figure 5 .
Figure 5. Green colour represents subpopulations with low risk of bias for the type of bias, yellow; moderate risk of bias, red; serious risk of bias and black; critical risk of bias.The distribution is weighted according to the size of each of the subpopulations.

Figure 7 .
Figure 7. Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 8 .
Figure 8. Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 9 .
Figure 9. Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 10 .
Figure 10.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 11 .
Figure 11.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 12 .
Figure 12.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 16 .
Figure 16.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 17 .
Figure 17.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 19 .
Figure 19.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 20 .
Figure 20.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 22 .
Figure 22.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

Figure 23 .
Figure 23.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

FIG. 25
FIG. 25 POOLED ESTIMATE AND FOREST PLOT OF STROKE EVENTS WITH SHORT-TERM FOLLOW UP ASSOCIATED WITH ONCE-ONLY COLONOSCOPY

Figure 26 .
Figure 26.Blue-coloured object: Studies without critical risk of bias, Red-coloured object: Studies with critical risk of bias, Black-coloured object: All studies regardless of the risk of bias.Circles: Randomized Controlled Trials, Squares: Non-randomized studies, diamonds: Weighted summary measures.The blue diamond shows the weighted average for studies that do not have a critical risk of bias.The red diamond shows the weighted average for studies with critical risk of bias.The black diamond shows the weighted average for all studies regardless of their risk of bias.

FIG. 28
FIG. 28 POOLED ESTIMATE AND FOREST PLOT OF ARRHYTHMIA WITH LONG-TERM FOLLOW UP ASSOCIATED WITH ONCE-ONLY COLONOSCOPY